Tobacco Documents Online

I confounding factor; however, the studies from Japan, where the diet is characteristically low in fat, show strong dose- response relationships for ETS and lung cancer. In addition, the study by Brownson et al. demonstrates lung cancer associations with both ETS2 and dietary fat3 in the highest exposure groups, yet finds no evidence that one factor confounds the other. The updated Fontham study4 also examined a number of dietary and other potential confounders, and concluded that "the strong association in this study between adult ETS exposure and lung cancer risk cannot be attributed to any likely confounder"4. 11. The CRS report says that two epidemiology studies that were published after the cutoff date for inclusion in the;EPA report find no statistically significant increased lung cancer risk (CRS-48 to CRS-49). The CRS then says that both studies found.a statistically significant increased risk in the highest exposure group, but that when large studies are "broken into several subsets and each is analyzed separately, some associations may be statistically significant by chance" (CRS-49). This comment does not reflect the consistency of the results for the highest exposure groups that the CRS notes two pages earlier;(CRS- 47). In addition, a third lung cancer studys that has come out since the EPA report, also showing an increased lung cancer risk in the highest expQsure group. Including the 3 new studies and the update of the Fonthan study4, all 20 studies that provide data by exposure group find an • increased lung cancer risk in the highest exnosure group, and 13 of these are statistically significant, despite the small sampld sizes. 12. The CRS report says that "many of the statistical concerns raised above with regard to lung cancer are relevant to raspiratory affects in children" (CRS-49). However, ~•Brownson et al. (1992) Passive smoking and lung cancer nonsmoking women. Am. J. Public Health s2:1525-1530. in .~ . 3 ALavanja at al. (1993) Saturated fat intake and lung cancer risk among nonsmoking women in Missouri. J. Natl. Cancer Inst. 85:1906-1916. ' Fontham at al. (1994) Environmental Tobacco Smoke and Lung Cancer in Nonsmoking Women: A Multicenter Study. JAMA 271:1752- 1759. j Liu at al. (1993) indoor air pollution and•lung cancer in GuangZhou, People's Republic of China. Am. J. Epidemiol. 137:145- 154. 12 I I I ~ I I I I I I I I I I I

I I I I I I I I I f I I I I I I I virtually none of the saae conce-Tns apply. i) The data on lower respiratory tract infections, for example, are even more consistent and show higher relative risk estimates than the lung cancer data. ii) TWo-tailed significance tests were used for the noncancer effects. iii) Smoker misclassi=ication is not an issue for infants.and young children. iv) The noncancer studies were not pooled, so no issues of weighting or subjective tiering apply. v) Parental smoking is generally a very good surrogate of total ETS exposure in young children. vi) With acute effects, there is little concern for uncertain exposures in the distant past, so exposure recall is less of a problem. vii) Several noncancer studies6 have biomarker evidence of ETS exposure, not just questionnaire data, and these biomarker data correlate with both the questionnaire data and the • health effects, alleviating concerns about recall bias and about the validity of questionnaire data. viii) Studies that have come out since the EPA report are not just consistent with, but actually go further than, the EPA's conclusions pertaining to noncancer effects''. 13. The CRS report raises the question of hypothetical confounding for the respiratory effects in children, saying that the "presence of other factors that may be related to these illnesses that are not controlled for are particularly i.mportant in the case of ... general respiratory illness, where the link between active smoking and disease is not as powerful as in the case of lung cancer" (Gts-49). The -absence of a link between active smoking and respiratory effects in adu?-zs has little biological relevance to respiratory effects in children since young children represent a highiy sensitive population because of their developing respiratory systems. As with lung cancer, the EPA did evaluate a number of potential confounding factors, and determined that they could not explain the observed associations. Furthermore, as with lung cancer, the consistent results observed across independent studies from 6 For example, Ehrlich et al. (1992) Childhood asthma and passive smoking: urinary cotinine as a biomarker of exposure. Am. Rev. Respir. Dis. 145:594-599; Etzel at al. (1992) Passive smoking and middle ear effusion among children in day care. Pediatrics 90:223-232; Reese et al. (1992) Relationship between urinary cotinine levels and diagnosis in children admitted to hosnital. Am. Rev. Respi. Dis. 146:66-70; Chilnonczyk et al. (1993) Association between exposure to environmental tobacco smoke and exacerbations of asthma in children. N. Engl. J. Med. 3z8:1665-1669- i 7 schoendorf and Kiely (1992) Relationship of sudden infant death syndrome on maternal smoking during and after pregnancy. Pediatrics 90:905-908. 13 I

I I a variety of countries, with different lifestyle factors, argue against confounding. E. EPA COM?iENTS ON T8E HEALTH EPPECTS COMPONENTS OF THE CH8 ASS.:SSME~.'T OF COSTS DIIE TO PAS&IVE SMOKING 1 Our comments relate only to the CRS's assumpticns pe~rtaining to the health effects of passive smoking, and do not address the economic basis for the CRS analysis. The'CRS derives cost estimates using three different methods, each of which raises concerns, which are detailed below:. 1. "Estimate based upon EPA's estimate of deaths from lung cancer" (CRS-11 to 12). In this case, the CRS multiplies the total costs per pack from active smoking by the ratio of lung cancer deaths attributed to passive smoking divided by the number attributed to active smoking. on the one hand, this overest:Lmates the costs per pack from passive smoking, because some of the active smoking costs do nflt apply to passive smoking, for example, the costs from fires and medical expenditures associated with emphysema. On the other hand, if the CRS is trying to estimate the costs forr all health effects that may be associated with passive smoking, a different ratio should be used. For example, 5teenland, in the same article cited by the CRS (CRS-22'and CRS-46), estimates that 35,000 to 40,000 heart disease deaths F er year in nonsmokers are attributable to passive smoking . Combining heart disease and lung cancer, which at least represent the two major causes of smoking-attributable mortality, yields a ratio of about 0.139, which is roughly six times higher than the ratio used by the CRS. Furthermore, the costs for respiratory effects in children from passive smoking should be added, because these are effects whose costs are not reflected in the total costs from active smoking. ~ 2. "Estimate based upon E?A's estimate of child hospitalizations" (CRS-12). Here, the CRS estimates the costs of•hospitalizations for children suffering from ET5- a Since the EPA has not assessed the role of ETS in heart disease, we are neither endorsing nor disavowing these estimates; we merely suggest that they be included for consistency in the cRs methodology. 9 37, 500 heart disease deaths plus 3, 000 lung cancer deaths per year attributable to passive smoking, divided by 313,000, the number of heart disease and lung cancer deaths attr:buted to active smoking in 1988 [MMtv"R (1991) 40 (4) : 63] . i 14 I I I I I I I I I I I I I I ~ .~. ~ [o Q O# V 0 I

I I I I I I I I I I. attributable lower respiratory tract infections. other costs for respiratory ei'fects in children resulting from passive smoking should be included, for example, hospitalizations for asthma attacks and for middle ear effusion, as well as costs of doctor visits and treat=ents for cases of lower respiratory tract infections, asthma, and middle ear effusion not requiring hospitalization. 3. "Estimate based upon relative physical exposure to smoke" (CRS-12). This method involves multiplying "the estimate of total active-smoking costs by the ratio of nonsmokers-to- smokers' physical exposure to smoke and by the ratio of nonsmoker to smokers" (CRS-12). The EPA-believes that estimates of passive smoking effects based on "physical exposure to smoke" extrapolated from active smoking to passive smoking, rather than on the epidemiology data for passive smoking, are erroneous. There is no scienti.fically valid ratio of "physical exposure to smoke" between active and passive smokers. The CRS uses the ratio of urinary cotinine, but cotinine is a metabolite of nicotine, which is just one of over 4,000 compounds in tobacco s;,ioke. Different comnounds yield different ratios and are associated with different health effects. Nicotine, in particular, is known to underestimate exposures to many other ETS toxicants, because it adheres readily to mciterials in indoor environments and is therefore more rapidly removed from contaminated air than are other constituents. Thus, nicotine is similarly likely to underestimate health risks when extrapolating from active to passive smoking. .  After adjusting for the "higher total active-smoking costs" . , estimated in the Manning study, the CRS states that its passive , smoking cost estimates "seem rather high" and attempts to, discount them First, it states that "the epidemiological evidence for passive-smoking-related disease is wea3c" (CRS-13). The EPA strongly disagrees with this statement ' as noted above (See Sections A-D). Second, the CRS states that "the estimates based upon physical exposure assume a linear relationship between exposure and disease" and that nonlinear relationships for health effects have been found with resaect to ' active smoking. As noted in #3 above, the EPA believes that the estimates based on physical exposure are unreliable because the concept of extrapolating "physical exposure to smoke" is flaWed. ~ Furt.hermore, as stated in i1 of Section D, the EPA disagrees with the statement that the relationships between exposure and health effects are "strongly nonlinear". The CRS cites as its basis , page 44 of the Surgeon General's 1989 Report (CRS-13). This reference pertains to one British study of active amoking, and lung cancer. The CRS report cites no evidence for nonlinear dose-response relationships for any other health eff ects and does ~ not address data from the many other studies of lung cancer and r~ zs ~ ~ ~ ~ ~ ~ I

I active smoking, including data from a much larger U.S. study that appear on the next page of the Surgeon General's Report, that suggest a linear relationship is reasonable. 16 I I I I I I I I I I I I I 1 I I